Evidenze di un possibile trattamento chirurgico in uno scheletro del sepolcreto di Casal Bertone (Roma, I-III sec. d.C.)

Nel corso dello scavo di Casal Bertone, che ha restituito oltre 200 sepolture è stato rinvenuto un individuo con evidenti alterazioni dei piedi. Le ossa tarsali risultavano fuse, i metatarsali avevano epifisi sfrangiate e cavità pseudocistiche e la tuberosità del calcagno destro era attraversata da un foro di dubbia eziologia. L’ individuo, d’età alla morte compresa tra 50 e 60 anni, di sesso femminile, è di corporatura gracile con una statura pari a 147 cm ca. Al fine di comprendere la patologia che aveva colpito l’individuo e la natura del foro del calcagno, gli elementi dei piedi sono stati sottoposti ad indagine tramite tomografia assiale computerizzata (TAC). Dalle immagini ottenute si osserva che la zona adiacente al foro presenta una radiopacità molto elevata dovuta alla calcificazione dell’osso; tale dettaglio suggerisce che il foro sia stato praticato in vita. L’ipotesi di un possibile intervento chirurgico potrebbe essere avvalorata dal rinvenimento di tracce d’argento all’interno del foro. Le fonti storiche riportano che alcuni strumenti chirurgici e contenitori utilizzati per miscelare i farmaci potevano esserne rivestiti; inoltre in età imperiale è attestato l’utilizzo dell’argento nelle ricette, come componente di farmaci e impiastri per il trattamento di alcune patologie.During the excavation of Casal Bertone an individual was found with evident alterations of the feet. The tarsal bones were fused, the metatarsals had fringed epiphysis and pseudocyst cavities and the tuberosity of the right calcane was crossed by a hole of dubious etiology. The individual, aged between 50 and 60 years old, of a female gender, is of a gracile body with a height of about 147 cm. ..............

Morphological evaluation of the placenta and fetal membranes during canine pregnancy from early implantation to term

To describe the histological changes of fetal adnexa throughout the physiological pregnancy, canine samples were obtained during natural delivery and caesarean section, as well as during ovariohysterectomy performed at any stage of undesired pregnancies (N=12). The first period of pregnancy (multiple samples collected at 10, 12, 14days) was consistent with pre- and peri-implantation events, i.e. apposition and initial invasion steps into the endometrium. The second period (multiple samples collected at 18, 38, 40, 45 days) was related to the development of extra-embryonic structures, placenta establishment and labyrinth formation. At the end of this period the maximum morphological complexity of the endotheliochorial placenta was achieved, characterized by complete erosion of the endometrial epithelium and underlying interstitium with exposure of maternal capillaries to the chorial cells. The third period of gestation (multiple samples collected at 50, 53, 57, 60, 63 days) was characterized by enhancement either of placental and extra-embryonic tissues

The maturation of HIV-1 protease precursor studied by discrete molecular dynamics

The equilibrium properties of a HIV-1-protease precursor are studied by means of an efficient molecular dynamics scheme, which allows for the simulation of the folding of the protein monomers and their dimerization into an active form and compare them with those of the mature protein. The results of the model provide, with atomic detail, an overall account of several experimental findings, including the NMR conformation of the mature dimer, the calorimetric properties of the system, the effects of the precursor tail on the dimerization constant, the secondary chemical shifts of the monomer, and the paramagnetic relaxation enhancement data associated with the conformations of the precursor. It is found that although the mature protein can dimerize in a unique, single way, the precursor populates several dimeric conformations in which monomers are always native-like, but their binding can be non-native

Identification and characterization of folding inhibitors of hen egg Lysozyme : an example of a new paradigm of drug design

Studies of protein folding indicate the presence of native contacts in the denatured state, giving rise to folding elements which contribute to the accomplishment of the native state. The possibility of finding molecules which can interact with specific folding elements of a target protein preventing it from reaching its native state, and hence from becoming biologically active, is particularly attractive. The notion that folding elements not only provide molecular recognition directing the folding process, but also have conserved sequence, implies that targeting such elements will make protein folding inhibitors less susceptible to mutations which, in many cases, abrogate drug effects. The folding-inhibition strategy can lead to a truly novel and rational approach to drug design, aside from providing new insight into folding. This is illustrated in the case of hen egg lysozyme

Identification and characterization of folding inhibitors of hen egg lysozyme : an example of a new paradigm of drug design

Studies of protein folding indicate the presence of native contacts in the denatured state, giving rise to folding elements which contribute to the accomplishment of the native state. The possibility of finding molecules which can interact with specific folding elements of a target protein preventing it from reaching its native state, and hence from becoming biologically active, is particularly attractive. The notion that folding elements not only provide molecular recognition directing the folding process, but also have conserved sequence, implies that targeting such elements will make protein folding inhibitors less susceptible to mutations which, in many cases, abrogate drug effects. The folding-inhibition strategy can lead to a truly novel and rational approach to drug design, aside from providing new insight into folding. This is illustrated in the case of hen egg lysozyme

Identification of the folding inhibitors of hen-egg lysozyme : gathering the right tools

The unfolded state of proteins displays a surprisingly rich amount of local native structure, which appears to be critical for driving the protein to its native state. Peptides with the same sequence of the corresponding structured segments can be used to interfere with the correct folding of the protein. Using model simulations, we investigate the folding of hen-egg lysozyme, identifying its key segments. Activity assays, NMR and circular dichroism experiments are used to screen the peptides which are able to inhibit the folding of lysozyme. Few peptides, corresponding to the segments of the protein which are structured in the unfolded state, are identified to have significant inhibitory effects

The complex folding behavior of HIV-1-protease monomer revealed by optical-tweezer single-molecule experiments and molecular dynamics simulations

We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and refolding process of a stable monomeric form of HIV-1-protease (PR). We have characterized the behavior under tension of the native state (N), and that of the ensemble of partially folded (PF) conformations the protein visits en route to N, which collectively act as a long-lived state controlling the slow kinetic phase of the folding process. Our results reveal a rich network of unfolding events, where the native state unfolds either in a two-state manner or by populating an intermediate state I, while the PF state unravels through a multitude of pathways, underscoring its structural heterogeneity. Refolding of mechanically denatured HIV-1-PR monomers is also a multiple-pathway process. Molecular dynamics simulations allowed us to gain insight into possible conformations the protein adopts along the unfolding pathways, and provide information regarding possible structural features of the PF state